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https://doi.org/10.3390/genes6010001
Title: | Down-regulation of miR-129-5p and the let-7 family in neuroendocrine tumors and metastases leads to up-regulation of their targets Egr1, G3bp1, Hmga2 and Bach1 | Authors: | Døssing, K.B.V Binderup, T Kaczkowski, B Jacobsen, A Rossing, M Winther, O Federspiel, B Knigge, U Kjær, A Friis-Hansen, L |
Keywords: | Bach1 protein early growth response factor 1 G3bp1 protein high mobility group A2 protein interstitial collagenase microRNA microRNA 129 protein transcription factor unclassified drug Article bone metastasis carcinogenesis clinical article controlled study down regulation growth inhibition human human cell human tissue immunohistochemistry in situ hybridization luciferase assay metastasis neuroendocrine tumor polymerase chain reaction primary tumor protein content protein expression protein targeting upregulation Western blotting |
Issue Date: | 2014 | Citation: | Døssing, K.B.V, Binderup, T, Kaczkowski, B, Jacobsen, A, Rossing, M, Winther, O, Federspiel, B, Knigge, U, Kjær, A, Friis-Hansen, L (2014). Down-regulation of miR-129-5p and the let-7 family in neuroendocrine tumors and metastases leads to up-regulation of their targets Egr1, G3bp1, Hmga2 and Bach1. Genes 6 (1) : 1-21. ScholarBank@NUS Repository. https://doi.org/10.3390/genes6010001 | Rights: | Attribution 4.0 International | Abstract: | Expression of miRNAs in Neuroendocrine Neoplasms (NEN) is poorly characterized. We therefore wanted to examine the miRNA expression in Neuroendocrine Tumors (NETs), and identify their targets and importance in NET carcinogenesis. miRNA expression in six NEN primary tumors, six NEN metastases and four normal intestinal tissues was characterized using miRNA arrays, and validated by in-situ hybridization and qPCR. Among the down-regulated miRNAs miR-129-5p and the let-7f/let-7 family, were selected for further characterization. Transfection of miR-129-5p inhibited growth of a pulmonary and an intestinal carcinoid cell line. Analysis of mRNA expression changes identified EGR1 and G3BP1 as miR-129-5p targets. They were validated by luciferase assay and western blotting, and found robustly expressed in NETs by immunohistochemistry. Knockdown of EGR1 and G3BP1 mimicked the growth inhibition induced by miR-129-5p. let-7 overexpression inhibited growth of carcinoid cell lines, and let-7 inhibition increased protein content of the transcription factor BACH1 and its targets MMP1 and HMGA2, all known to promote bone metastases. Immunohistochemistry analysis revealed that let-7 targets are highly expressed in NETs and metastases. We found down-regulation of miR-129-5p and the let-7 family, and identified new neuroendocrine specific targets for these miRNAs, which contributes to the growth and metastatic potential of these tumors. © 2014 by the authors; licensee MDPI, Basel, Switzerland. | Source Title: | Genes | URI: | https://scholarbank.nus.edu.sg/handle/10635/182039 | ISSN: | 20734425 | DOI: | 10.3390/genes6010001 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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